Background: Stressful life experiences frequently precede the onset of major depression; however, the mechanisms that underlie this link are poorly understood. Importantly, some individuals are more susceptible to the depressogenic effects of stress than others. Carriers of the S or LG allele of the 5-HTTLPR/rs25531 polymorphisms (S’ participants) have been found to be more prone to developing depression under stress relative to L or LA homozygotes (L’ participants). Moreover, emerging evidence indicates that stress-induced anhedonia may be a mechanism underlying links between stress and depression. Given these findings, we hypothesized that exposure to a naturalistic stressor (school final examinations) would disrupt reward responsiveness (a key behavioral component of anhedonia), and that this effect would be strongest in S’ participants. Methods: To objectively assess reward responsiveness, we administered a probabilistic reward task to 70 Bulgarian high school students over two sessions in the 6-month period preceding school finals. For each participant, the two sessions were designated as the ‘stress’ and ‘control’ conditions based on self-reported perceived stress. Results: A genotype × condition interaction emerged in males, with S’ participants showing larger stress-related reduction in reward responsiveness relative to L’ participants. Conclusion: While in need of replication in a larger sample, our results indicate that stress associated with a real-life event is linked to reduced reward responsiveness, the susceptibility to which is modulated by 5-HTTLPR/rs25531 genotype. Although preliminary, these findings identify anhedonia as a promising mechanism linking 5-HTTLPR/rs25531 genotype and stress to depression.
© 2011 S. Karger AG, Basel
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Diego A. Pizzagalli
Center for Depression, Anxiety and Stress Research
Room 233C, McLean Hospital
115 Mill Street, Belmont, MA 02478 (USA)
Tel. +1 617 855 4230, E-Mail firstname.lastname@example.org
Received: January 21, 2011
Accepted after revision: May 5, 2011
Published online: November 17, 2011
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 1, Number of References : 62
Neuropsychobiology (International Journal of Experimental and Clinical Research in Biological Psychiatry, Pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography)
Vol. 65, No. 1, Year 2012 (Cover Date: December 2011)
Journal Editor: Strik W. (Bern)
ISSN: 0302-282X (Print), eISSN: 1423-0224 (Online)
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